Mass spectrometry is a powerful analytical tool used in the identification of unknown compounds and elements. The technique measures the mass-to-charge ratio (m/z) of individual ionized molecules. Because the charge of those ions is usually known (and is usually plus or minus z, the charge of one electron), the mass of the ion may be deduced, and the molecule may be generally identified.
A functional block diagram of a modem mass spectrometer 100 is shown in FIG. 1. An inlet 110 provides a location for introduction of a sample. The inlet may be configured to accept a solid, a liquid or a gas. The inlet is equipped to permit introduction of the sample into a vacuum chamber 150 that is kept evacuated using vacuum pumps 118.
The sample passes into an ion source 112 that provides the charged molecular particles that are to be detected. In a commonly-used source known as an electron ionization (EI) source or electron impact source, ions are generated by bombarding a gaseous sample with a beam of energetic electrons. Solids and liquids may first be vaporized by evaporation or sublimation, then subject to EI. While the EI process is simple, it can result in the decomposition of the molecules to be tested. It is then necessary to indirectly deduce the original composition of the sample, often with ambiguous results.
A number of lower energy or “soft” ionization techniques have been developed based on chemical or desorption ionization. Chemical ionization produces ions by the relatively low energy process of proton transfer. The sample molecules are exposed to a large excess of ionized reagent gas, and protons are transferred from the reagent to the sample molecules to produce positive ions. Negative ions have also been produced by transferring a proton from the sample molecule to the reagent. Low energy electrons have also been added to sample molecules by collisionally reducing the energy of the electrons generated in the source.
Desorption ionization is a process by which a molecule is both evaporated from a surface and ionized. The process may involve bombarding the surface with high energy particles or subjecting the surface to a high intensity electric field.
The ions produced by the ion source 112 are separated by an analyzer 114 where the ions are sorted according to their mass-to-charge ratio. The sorted ions are then processed by a detector 116, where ion flux is converted into a proportional electrical current. That electrical current is recorded and analyzed by a data processing system 120 that contains analysis algorithms for producing mass spectra data outputs 122.
Several techniques have evolved for sorting and detecting ions in a modern mass spectrometer. The most widely used of those techniques include magnetic sector analyzers, quadrupole mass filters, quadrupole ion traps, Fourier transform ion cyclotron resonance spectrometers and time-of-flight mass analyzers. Of those techniques, a well-designed Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) provides extremely high resolution for relatively low cost.
Most mass spectrometers operate by altering the trajectory of an ion in a magnetic field. The new trajectory depends on properties related to the mass-to-charge ratio of the ion; i.e., at a given velocity, the trajectory of a more massive ion is altered less than that of a less massive ion. By subjecting ions of differing m/z to a fixed magnetic field, those ions may be separated for detection and analysis.
A cell or chamber 200 of a typical FT-ICR MS, shown in partial section in FIG. 2, includes a group of plates 211–216 surrounding a roughly cubic cell 225. Ions may either be generated externally and introduced along path 250, or are generated within the cell. The ions are trapped electrostatically in a homogeneous magnetic field 220. The ions orbit around the field lines in orbits 230. Trapping plates 215, 216 keep the ions from spreading along the field lines.
The orbital motion 230 is induced by applying an RF pulse to the excitation plates 213, 214. Ions having a particular mass are excited by a particular resonant frequency, with less massive ions having a higher resonant frequency and more massive ions having a lower resonant frequency. In practice, a short RF pulse containing a specific group or range of frequencies is applied across the excitation plates 213, 214 to move all the ions sequentially.
As the ions are excited by their respective resonant frequencies, the orbit 230 of those ions enlarges, bringing them in proximity with the detection plates 211, 212. The ions induce a faint signal across the plates, which is received and analyzed by data system 120 (FIG. 1). Alternatively, the orbit of selected ions can be enlarged to a diameter that exceeds the dimensions of the cell by increasing the amplitude of the signal at the resonant frequency. This process, known as ejection, brings the selected ions outside the cell where they are eliminated by the vacuum pump. The ejection process is used to eliminate ions of chosen m/z to improve the detection limit of other ions, particularly when the concentration of the ejected ions is large compared to that of the ions of interest. For example, ejection may be used in detecting gasses in trace amounts with hydrogen.
The electronics 300 of an FT-ICR MS, shown as a simplified schematic in FIG. 3, includes detection electronics 310, excitation electronics 350 and a computer control 380. The excitation electronics 350 includes a digital signal processor (DSP) 352 controlling a digital to analog converter (DAC) 354. The output from the DAC 354 is filtered by filter 356 to remove unwanted signal components. The DSP 352, DAC 354 and filter 356 are used in existing FT-ICR MS equipment for the excitation and ejection of particles having a moderate to large molecular mass. The DAC 354 is controlled to generate a waveform containing the resonant frequencies used to excite or eject components that have masses corresponding to those resonant frequencies. An arbitrary waveform generator 358 is alternatively used in some applications. In either case, the waveform is applied across the excitation plates 213, 214 of the FT-ICR MS cell 200.
Detection electronics 310 receive the resulting signal from the detection plates 211, 212. An analog-to-digital converter (ADC) 317 converts the analog signal to a digital signal, which is processed by the DSP 315.
Process control electronics 386 send signals to control elements of the test equipment such as process valving and vacuum pumps, shown schematically as a single element 385. In that way the timing and sequence of events in the test process can be closely controlled.
The excitation electronics 350, detection electronics 310 and process control electronics 386 are controlled by a computer control 380. The computer control 380 executes instructions for initiating and operating the excitation and detection electronics 350, 310 and performing the Fourier transformations, as well as initiating and operating the process control electronics, and stores data for running particular routines involving those components. The computer control also stores and performs analysis of data received from the detection electronics 310.
Because the basic principles used in mass spectroscopy separate ions based on their mass-to-charge ratio, the technique is inherently limited in cases where the sample mixture contains compounds having similar atomic masses. For example, in the case of a hydrocarbon mixture in which isomers such as butene and cyclobutane are present, those compounds cannot be distinguished based solely on mass, because both have compositions C4H8 and atomic weights of 56. Yet, because of the markedly different physical properties of those two isomers, it is often important to quantify their presence in a hydrocarbon mixture.
One approach to that problem is the coupling of gas chromatography (GC) to mass spectrometry. That connection allows compounds already in the vapor phase to enter the mass spectrometer separated in time so that the components of mixtures can be detected and analyzed sequentially. More recently, liquid chromatographs, supercritical fluid chromatographs, and capillary electrophoresis devices connected to mass spectrometers have been used to separate components of complex mixtures prior to mass analysis. The use of those techniques, however, it often extremely time consuming. For that reason, those techniques cannot be used on-line for real-time process control. Furthermore, those techniques, when coupled to mass spectrometry, often do not yield reliable quantification of the mixture components. That limitation also makes chromatography only marginally useful in on-line applications.
Charge exchange reactions are known. In a charge exchange reaction, an ionic reagent having an ionization potential x is associated with a sample compound having an ionization potential y where x>y. Because the energy released by neutralizing the reagent is greater than the energy required to ionize the sample, the reaction is exothermic. In a sample containing compounds having various ionization potentials, compounds that have an ionization potential greater than x are not ionized.
Charge exchange reactions have been described in connection with gas chromatography and mass spectroscopy. One such description is by Brian Wagner, Gordon Nicol & Burnaby Munson, “Fast Quantitation of BTEX and Total Aromatics in Petroleum Products by GC/CIMS,” 1999 ASMS Conference Proceedings. The authors disclose the use of a low energy charge exchange reaction as a method for selective ionization of the aromatic components in petroleum products. The charge exchange reaction is coupled with gas chromatography to selectively produce ions that are then introduced into the analyzer and detector cells of a quadrupole mass spectrometer. Cycle time is said to be reduced to about 15 minutes. Such a cycle time still far exceeds that required for on-line, real time process control.
There is therefore presently a need to provide a method and apparatus for the on-line detection and accurate quantization of multiple isomers in a mixture. Particularly, there is a need for a technique for use with a FT-ICR mass spectrometer that permits the discrimination of isomers without a great increase in cycle time. The technique should preferably be implemented with a minimum of additional cost. To the inventor's knowledge, there is currently no such technique available.